If you are like many of the 14 million men in the United States who have been diagnosed with benign prostatic hyperplasia (BPH), you’ve probably been taking the same medication, at the same dose, for years. If so, consider the experiences of two patients, both of whom were taking some type of medication for BPH. Their names have been changed, but all other details are accurate (see “Jack Muriel” and “Henry Banks” below).
At 64, Jack was taking tamsulosin (Flomax) for moderate BPH but otherwise was in good health. Recently retired, he looked forward to a weekly round of golf with friends at a local country club. One evening, while driving home to meet his wife for dinner, Jack suddenly became lightheaded. He felt as if he were about to faint. He managed to pull the car over to the side of the road and call for help. While dialing, he thought, “Maybe I shouldn’t have taken the Viagra and Flomax at the same time.”
At 77, Henry was generally in good health, but had been taking terazosin (Hytrin) for his BPH for years. At one point, after Henry experienced a bout of unexplained abdominal pain, his internist ordered an abdominal CT scan to determine the problem. As instructed by the radiology department, Henry drank large quantities of water before the procedure. The CT scan itself went fine, but afterward, Henry found he could not urinate, even though his bladder was full. Instead of returning home after the CT scan, Henry wound up in the emergency room, where he had to have a catheter inserted.
Jack and Henry experienced unexpected consequences while taking a BPH medication. Fortunately none of these consequences had long-lasting health effects — and they could be avoided in the future by making some adjustments. In Jack’s case, the problem was mixing a BPH medication with one for erectile dysfunction. Although many men use both medications without difficulty, some may need to take precautions. Henry might have been able to avoid a visit to the emergency room if, before getting a computed tomography (CT) scan, he’d told the radiologist that he had been taking a medication for severe BPH.
Certainly some type of adverse event, such as these men experienced, might make you wonder if it’s time to adjust the dose of your medication or perhaps even change medications. But there are other considerations as well. Every man is different. In this article, you’ll learn about the types of issues many men with BPH have confronted, and what situations might indicate it’s time to consider a change in medication.
Issues to consider
The two classes of drugs currently approved to treat BPH — alpha-1 blockers and 5–alpha-reductase inhibitors — work in entirely different ways, and therefore raise different types of issues. So it’s important to understand these differences as you evaluate which medications might be right for you.
Simply put, alpha-1 blockers deal with the “going” problem by relaxing certain muscles in the prostate and urinary tract, while 5–alpha-reductase inhibitors deal with the “growing” problem by reducing the size of the prostate (see Figure 1).
Figure 1. How BPH medications work
A. As the prostate gland enlarges, it constricts the urethra, which carries urine out of the body, and may expand up into the bladder itself. This not only impedes urinary tract functioning, but also reduces the volume of urine the bladder can hold.
B. Alpha-1 blockers attach to certain receptors in the muscle walls — much as a key fits into a lock. By blocking alpha-1 receptors, alpha-1 blockers prevent insertion of the chemical keys that signal a muscle to contract. The muscles relax and urine flows more freely.
C. The 5–alpha-reductase inhibitors have a different mechanism of action: They neutralize 5–alpha reductase, the enzyme that initiates conversion of testosterone into dihydrotestosterone, or DHT, the form of the hormone that is usable in the prostate. By blocking the action of the chief male hormone responsible for growth of the prostate, these drugs eventually cause the prostate to shrink.
The alpha-1 blockers are classed into two groups. The selective agents, alfuzosin (Uroxatral), silodosin (Rapaflo), and tamsulosin (Flomax, generic), work primarily on the tissues of the urinary tract. The nonselective agents, doxazosin (Cardura, generic) and terazosin (Hytrin, generic), affect both the urinary tract and other tissues elsewhere in the body. The 5–alpha-reductase inhibitors, which include dutasteride (Avodart) and finasteride (Proscar, generic), act directly on the prostate.
Other medications are in development (see “Anticholinergic drugs” and “PDE-5 inhibitors,” below), but are not yet available. So for now, you’ll have to weigh the relative risks and benefits of alpha-1 blockers and 5–alpha-reductase inhibitors.
These medications are used to quiet overactive bladder muscles, which can lead to urinary incontinence. Investigators have discovered in the past few years that more than half of men with BPH also suffer from overactive bladder, and that this may further exacerbate urinary difficulties. Researchers are now investigating whether taking anticholinergic drugs can ease BPH symptoms.
When it comes to recommending one drug or another, urologists often use some general guidelines: Alpha-1 blockers are better at relieving urinary symptoms such as difficult or frequent urination, and are best for men with smaller prostate glands. But 5–alpha-reductase inhibitors may be in order if you have a large prostate gland or have not obtained sufficient relief from alpha-1 blockers. And they have a stronger track record for reducing the chance that you’ll need surgery or will experience complications such as acute urinary retention. Sometimes the medications are prescribed in combination.
Time to change?
Any of the following suggests that you should re-evaluate your BPH medication:
Speed of relief
The alpha-1 blockers work quickly, taking effect in days to weeks. But the nonselective agents may require some patience, as doses have to be increased slowly at first, to avoid lowering your blood pressure too much. Doctors usually start with 1 milligram (mg) at bedtime, then gradually increase it as needed to a maximum of 10 mg of terazosin or 8 mg of doxazosin. This process, known as titration, may be frustrating for you as well because you will need to wait to find the correct therapeutic dose.
Dosing is simpler for the selective alpha-1 blockers. For tamsulosin, you take 0.4 mg or 0.8 mg half an hour after dinner. Alfuzosin is a time-release formulation, so a single 10-mg tablet is taken once a day immediately after a meal.
With the 5–alpha-reductase inhibitors, it takes longer to feel the results. These drugs shrink the prostate by reducing levels of the male hormone dihydrotestosterone (DHT), which promotes prostate growth. Levels of DHT fall precipitously after several weeks of taking a 5–alpha-reductase inhibitor, but it may take at least three to six months, and perhaps even longer, before you notice any improvement in urine flow.
When it comes to BPH, are two drugs better than one? The Medical Therapy of Prostatic Symptoms (MTOPS) study indicated that the answer may be yes — at least for some men. In the study, 3,047 men with BPH were randomly assigned to take doxazosin (Cardura), finasteride (Proscar), a combination of the two, or a placebo. After roughly four and a half years of observation, the combination reduced the risk of BPH progression (symptoms getting worse) by 66% when compared with placebo, significantly more than either drug alone. Compared with placebo, doxazosin reduced BPH progression by 39%, and finasteride reduced it by 34%.
A 2006 reanalysis of the MTOPS data according to prostate gland size found that combination therapy provided the most benefit to men whose prostate glands were 25 grams or greater in size (see “MTOPS study and reanalysis,” below).
MTOPS study and reanalysis
McConnell JD, Roehrborn CG, Bautista OM, et al. The Long-Term Effect of Doxazosin, Finasteride, and Combination Therapy on the Clinical Progression of Benign Prostatic Hyperplasia. New England Journal of Medicine 2003;349:2387–98. PMID: 14681504.
Marberger M. The MTOPS Study: New Findings, New Insights, and Clinical Implications for the Management of BPH. European Urology Supplements 2006;5:628–33.
Some men with large prostates try combination therapy to get fast relief for their symptoms from the alpha-1 blockers. In six months or so, when the 5–alpha-reductase inhibitors begin taking effect, these men may stop taking the alpha-1 blockers.
However, you should consider two additional pieces of information when contemplating whether to start combination therapy: cost and side effects. First, taking two pills is more expensive. If you have to pay for medications on your own, or if your insurance company requires some type of co-pay, you may want to figure cost into the equation. Second, although the MTOPS study found that side effects were similar whether men took one drug or the combination, many experts feel differently, based on the patients they see.
High blood pressure
The nonselective alpha-1 blockers block alpha receptors in the heart and blood vessels as well as in the prostate, lowering blood pressure in the process. While these agents are usually not the first choice for blood pressure control, they may be a good choice for men who have both BPH and high blood pressure. If you want to limit the number of different medications you are taking, ask your doctor whether using a nonselective alpha-1 blocker might enable you to control both your BPH and your blood pressure — and then monitor both your urinary symptoms and your blood pressure to make sure the medicine is really working for you.
If you are already on another medication to control your blood pressure, or are taking an erectile dysfunction drug, then taking a nonselective alpha-1 blocker carries the risk that you will experience lightheadedness, faintness, dizziness, or postural hypotension (a drop in blood pressure that occurs when you sit or stand quickly, as when getting up from a chair or out of bed). Although a panel of Harvard experts thought the risk of hypotension was minimal, it’s still worth knowing about. Sudden episodes of low blood pressure can be dangerous if you already have some type of vascular disease, because it increases your risk of suffering a heart attack or stroke.
Similarly, because of these side effects, the nonselective alpha-1 blockers may not be the best choice for you if your blood pressure is already on the low side.
The selective alpha-1 blockers, alfuzosin, silodosin, and tamsulosin, have less of an impact on blood pressure, so they may be good alternatives in these situations. (Men taking silodosin may notice a drop in blood pressure upon standing.) Or consider taking a 5–alpha-reductase inhibitor.
The nonselective alpha-1 blockers (doxazosin and terazosin) are available now in generic as well as brand name formulations, and so may save you some money (see Table 1). Of course this may also depend on what type of drug coverage is included in your health insurance plan, and how much of a co-pay you need to contribute.
Table 1. Cost of BPH drugs compared
The costs below are based on average wholesale prices to pharmacists and the lowest dosage; costs to patients may be more.
|Drug class||Generic name (brand name)||Estimated cost per month for generic, if available||Estimated cost per month for brand name medication|
|Nonselective alpha-1 blockers||doxazosin (Cardura), 1-mg tablets||$17.99||$51.67|
|terazosin (Hytrin), 10-mg tablets||$13.99||n/a|
|Selective alpha-1 blockers||alfuzosin (Uroxatral), 10-mg tablets||n/a||$129.16|
|silodosin (Rapaflo), 8-mg capsules||n/a||$124.99|
|tamsulosin (Flomax), 0.4-mg tablets||$120.99||$142.18|
|5–alpha-reductase inhibitors||dutasteride (Avodart), 0.5-mg capsules||n/a||$123.57|
|finasteride (Proscar), 5-mg tablets||$70.08||$112.99|
|Prices given are those charged by the online retailer drugstore.com as of Oct. 1, 2010 for a one-month supply (30 capsules or tablets). They do not take any discounts or insurance coverage into consideration. Drug prices may vary, and your pharmacy may charge more.|
Sexual side effects
Because they affect levels of the male hormone testosterone, the 5–alpha-reductase inhibitors may cause a variety of sexual side effects. In the original clinical trials, 3.7% of men taking these drugs (and 4%–6% by some other estimates) developed erectile dysfunction. Another 3.3% of men experienced a decline in libido, while 2.8% had problems ejaculating during an orgasm.
In addition, one of the selective alpha-1 blockers, tamsulosin, causes ejaculation problems in some men who take it. The other alpha-1 blockers may cause less of this problem.
Erectile dysfunction is treatable with three medications, and it is generally safe to take these drugs when you are taking your BPH medication, whether it is an alpha-1 blocker or a 5–alpha-reductase inhibitor; however, we offer some important cautionary advice.
If you develop problems with ejaculation during sex, the solution depends on what medication you are taking. If you are taking a 5–alpha-reductase inhibitor, the only way to resolve the ejaculation difficulties is to stop taking the BPH medication, so you may need to decide on another medication (or surgery) to deal with your urinary difficulties. However, if you are taking tamsulosin, you may be able to alleviate ejaculation problems by taking the drug every other day (see “Alternate days,” below).
Investigators asked 140 men with BPH to take 0.4 mg of tamsulosin (Flomax) daily for three months. If the men responded to tamsulosin, they were randomized to one of three groups. One group continued taking the medication daily, the second took the same dose every other day, and the third stopped taking the drug. Men taking tamsulosin every other day did just as well as those taking it daily, and experienced fewer side effects such as ejaculation problems.
Source: Yanardag H, Goktas S, Kibar Y, et al. Intermittent Tamsulosin Therapy in Men with Lower Urinary Tract Symptoms. Journal of Urology 2005;173:155–7. PMID: 15592062.
Gynecomastia (breast enlargement), another possible side effect of the 5–alpha-reductase inhibitors, is rare but is distressing when it occurs. Stopping the medication may reverse the problem. But not always: Some men have had to undergo breast reduction surgery — or learn to live with the changes.
Medications for erectile dysfunction
Three medications have been approved for the treatment of erectile dysfunction: sildenafil (Viagra), tadalafil (Cialis), and vardenafil (Levitra). These medications are all PDE-5 inhibitors, which generate nitric oxide, a chemical that enables arteries to widen. The increased blood flow to the penis helps to produce an erection. The problem is that arteries elsewhere in the body widen as well, causing a slight drop in blood pressure.
If you are considering an erectile dysfunction medication, you don’t have to worry if you are also on one of the 5–alpha-reductase inhibitors for your BPH: The drugs can be taken together without adverse effects. However, if you are currently using, or considering, an alpha-1 blocker, you may want to take some precautions when adding one of the PDE-5 inhibitors.
Here’s why: Because the PDE-5 inhibitors cause a system-wide drop in blood pressure, theoretically they can exacerbate the blood pressure–lowering action of the nonselective alpha-1 blockers doxazosin and terazosin. This seems especially to be a problem when taking sildenafil (Viagra) and vardenafil (Levitra); tadalafil (Cialis) is a longer-acting PDE-5 inhibitor, and the risks are less clear.
As a result, some doctors recommend that if you are using a nonselective alpha-1 blocker for BPH, you should avoid taking an erectile dysfunction medication altogether. However, our panel of Harvard experts think the concerns are overblown. If you don’t want to stop using a nonselective alpha-1 blocker for your BPH, you can make sure you take the PDE-5 inhibitor at different times of the day (take one medication after lunch, say, and the other in the evening) to avoid problems.
Or you can lower the dose of your alpha-1 blocker or PDE-5 inhibitor. That is what Jack Muriel eventually decided to do. He’d taken his BPH medication, Flomax, along with Viagra before heading home to have dinner with his wife. The combination created the dizziness that caused him nearly to run off the road. His doctor suggested he try lowering his dose of Viagra in the future, to 25 mg (from the 100–200 mg he’d been taking), because that would lessen the chance of dizziness if he took it along with the Flomax. Or, if that dose was not sufficient, he could try 50 mg of Viagra. But to prevent problems, he needed to make sure that he took it at least four hours before (or after) he took the Flomax.
Could these medications, already approved to treat erectile dysfunction, also alleviate BPH symptoms? The answer may be yes, according to early studies of sildenafil (Viagra) and tadalafil (Cialis) — although the dosing is different than for erectile dysfunction. The medications may help by relaxing smooth muscle within the prostate, thereby improving the flow of urine. However, more research is needed.
The Prostate Cancer Prevention Trial showed that taking one of the 5–alpha-reductase inhibitors, finasteride, reduced the risk of developing prostate cancer by 24.8% — an astounding amount, and a result that would normally change the practice of medicine.
But here’s the bad news — and why you need to consider your choice of finasteride carefully: Men in the study who took finasteride were more likely to develop high-grade cancer (the type more likely to spread and become life-threatening) than those taking a placebo. In the PCPT study, high-grade prostate cancers developed in 37% of the men taking finasteride who developed tumors (6.4% of all the men taking finasteride), compared with 22% of the men taking placebo who developed tumors (5.1% of all men taking placebo).
So what’s going on? It’s not clear. The PCPT study has generated heated discussion, and one leading theory is that because finasteride shrank the prostate gland, doctors had a smaller target to sample, and were therefore more likely to find cancer. It is unclear whether the findings also apply to dutasteride, but because the drug is in the same class, most researchers think it does. For now, check with your own urologist for advice about what you should do.
Pay attention to PSA levels. If you decide to take a 5–alpha-reductase inhibitor, whether it’s only for your BPH symptoms or because you also want to reduce your overall risk of prostate cancer, you’ll need to understand how these medications will affect your PSA levels. In general, 5–alpha-reductase inhibitors tend to reduce PSA levels by about 50%, although the actual reduction varies from man to man. It is important to obtain a baseline PSA value before beginning treatment with one of these medications, and then have another after 6–12 months, to see how much the PSA has gone down after treatment. This follow-up PSA then becomes your new baseline.
You’ll need to figure this new baseline into your calculations as you monitor your PSA in the future. So, for example, if you start taking a 5–alpha-reductase inhibitor, and your PSA falls from 3 to 1.5, that’s to be expected. But if it should double over the course of a year, say from 1.5 back to 3, talk with your doctor about whether to have a prostate biopsy. Even though a value of 3 is considered “normal” in men not taking a 5–alpha-reductase inhibitor, a PSA value that doubles within a year of beginning one of these medications could indicate that cancer is present.
Acute urinary retention
Henry Banks developed acute urinary retention after drinking large quantities of water for a CT scan. This is a medical emergency, because if someone is unable to urinate and excrete urine, over time pressure that builds up in the bladder can adversely affect the kidneys, possibly leading to kidney failure — which is life-threatening.
For most men, of course, the most tangible worry about acute urinary retention is that they may have to have a catheter inserted to relieve pressure on their bladder — which is simply uncomfortable, bothersome, and potentially embarrassing (the catheter can sometimes leak, causing accidents). Sometimes a man can be weaned from the catheter and return to taking a BPH medication, but not always. A man who has developed acute urinary retention may need to consider surgical options to alleviate his symptoms.
Although BPH symptoms often remain stable, one study found that progression was likely in men with the following clinical profile:
Source: Crawford ED, Wilson SS, McConnell JD, et al. Baseline Factors as Predictors of Clinical Progression of Benign Prostatic Hyperplasia in Men Treated with Placebo. Journal of Urology 2006;175:1422–7. PMID: 16516013
To reduce your risk of developing acute urinary retention, you have two options. The first is to take some common-sense precautions, no matter what BPH medication you are on. Watch your intake of fluids, especially if you will be unable to urinate for a while (such as when you’re at a sporting event or on a long airplane trip). If your doctor recommends a medical test that requires you to drink fluids ahead of time, as Henry did, mention that you are taking a BPH medication and ask what your doctor advises.
Second, if you are at risk for acute urinary retention, it means your symptoms have progressed so that your urinary difficulties are moderate to severe in intensity (see “BPH progression,” above). It may be time to consider switching to a 5–alpha-reductase inhibitor. Because these medications reduce the size of the prostate and thus ease constriction of the urethra, they also reduce the risk of developing acute urinary retention and having to undergo surgery (see “Two additional benefits,” below).
Two additional benefits
A clinical trial involving more than 3,000 men, comparing finasteride (Proscar) with placebo, found that only 3% of men taking finasteride developed acute urinary retention (versus 7% taking placebo), and 5% eventually required surgery (versus 10% taking placebo).
Source: McConnell JD, Bruskewitz R, Walsh P, et al. The Effect of Finasteride on the Risk of Acute Urinary Retention and the Need for Surgical Treatment Among Men with Benign Prostatic Hyperplasia. New England Journal of Medicine 1998;338:557–63. PMID: 9475762.
Making a decision
Obviously the decision about whether to make some change in your medication regimen for BPH — whether it involves changing the dose or switching medications — is a complex one. You alone know how bad your urinary symptoms are, and what other health issues and trade-offs you need to consider.
Table 2 summarizes the salient information by drug and suggests the type of men who might want to consider taking one drug rather than another. Ultimately, of course, you are the authority when it comes to your own body, and different people metabolize drugs in different ways, so these general guidelines should be viewed as just that — general.
Even so, the information in this table, and in the rest of this article, may help you clearly evaluate your medication options. And if you ultimately decide that medications are not providing you with sufficient relief, it may be time to look into surgical options.
Table 2. General guidelines for BPH medications
|Medication and mechanism of action||Potential side effects||You might want to consider using if||You may not want to use if|
|Alpha-1 blockers (nonselective)
doxazosin (Cardura, generic)
terazosin (Hytrin, generic)
How they work
|Alpha-1 blockers (selective)
tamsulosin (Flomax, generic)
How they work
finasteride (Proscar, generic)
How they work
Originally published Jan. 1, 2007; last reviewed April 22, 2011.